It is the broad, long-term goal of this program to build on and extend the current knowledge in the field of bone marrow transplantafion and hematological malignancies. This program is a mulfidisciplinary clinical, basic and translational research effort whose overall goal is to improve outcomes for patients with solid and liquid malignancies. To this end, the investigators of this application will ufilize the approach of translational research, bridging the novel experimental concepts and observations made at the laboratory bench to clinical applicafion at the pafients' bedsides. In both basic and clinical areas, the HCTHM Program fosters interacfions between many Programs and members of the DCCI. The Program includes 35 members from 11 basic and clinical departments within Duke University. Total funding for program members is $68,881,117, of which $64,009,143 is from peer- reviewed sources. A cancer focus is illustrated by $976,102 or 1.5% of funding from the NCI, the American Cancer Society or the Department of Defense. From 2004- 2008, program members published 706 papers in peer-reviewed journals cited in PubMed. Of these publicafions, 6.4% are the result of intra-programmatic collaborations and 13% due to inter-programmafic collaborations. The aims of the Program are: 1. To optimize the use of allogeneic and autologous transplantation of hematopoiefic stem cells. 2. To use and compare various alternative sources of hematopoietic stem cells for allogeneic transplantation. 3. To develop novel preparatory regimens for allogeneic stem cell transplantation. 4. To understand the basic biology of graft versus tumor (GvT) and to explore new ways to induce GvT effects following transplantation. 5. To study the nature of and define the problems associated with hematopoiefic and immunologic reconstitution after allogeneic transplantation with the overall goal of developing novel supportive care measures for patients transplanted with stem cells from alternative and mismatched donors. 6. To understand hematopoietic stem cell development and control of differentiation. 7. To promote effective interactions of the members of the Duke Comprehensive Cancer Institute that will stimulate new translational research efforts to improve the care of patients with hematologic malignancies. 8. To identify new cellular and stromal targets for therapy with antibodies or small molecules, leading to evaluafion of various labeling techniques, such as using radiolabels or diphtheria toxins, of small molecules and antibodies with subsequent clinical evaluation of safety and efficacy. 9. To evaluate the importance of different signaling mechanisms in leukemogenesis or lymphomagenesis.